Physico-chemical properties and reactive oxygen species generation by respirable coal dust: Implication for human health risk assessment.

This study investigates the mineralogy, micro-morphology, chemical characteristics and oxidation toxicity of respirable dusts generated in underground coal mines. The active sampling was applied to collect airborne particulates with aerodynamic diameter <4 µm (PM4) at depth greater than 500 m from earth surface. The average mass concentration of PM4 was extremely higher than recommended values. QXRD and FESEM-EDS analyses were applied to study the micro-mineralogy and micro-morphology of respirable dusts. The chemical analysis by ICP-MS revealed an enrichment of V, Cr, Cu, Zn, As, Ag, Cd and Sb in respirable dust compared with the background environment and world coals. The EPA's health risk model showed that the health risk posed by Cr and Co in all workplaces exceeded the acceptable risk value for human health. The synthetic respiratory tract lining fluid (RTLF) model was utilized to achieve a novel insight into the toxicity of respirable coal dust. The result showed an overall depletion of lung surface antioxidants with the decreasing trend of ascorbic acid > reduced glutathione >> urate, implying low- to medium level of oxidative stress. The result of this study can be applied globally by decision-makers to decrease hazardous exposure of mine workers to respirable dust.

Setting research priorities to achieve long-term health targets in Iran.

BACKGROUND: In 2015, it was estimated that the burden of disease in Iran comprised of 19 million disability-adjusted life years (DALYs), 74% of which were due to non-communicable diseases (NCDs). The observed leading causes of death were cardiovascular diseases (41.9%), neoplasms (14.9%), and road traffic injuries (7.4%). Even so, the health research investment in Iran continues to remain limited. This study aims to identify national health research priorities in Iran for the next five years to assist the efficient use of resources towards achieving the long-term health targets. METHODS: Adapting the Child Health and Nutrition Research Initiative (CHNRI) method, this study engaged 48 prominent Iranian academic leaders in the areas related to Iran's long-term health targets, a group of research funders and policy makers, and 68 stakeholders from the wider society. 128 proposed research questions were scored independently using a set of five criteria: feasibility, impact on health, impact on economy, capacity building, and equity. FINDINGS: The top-10 priorities were focused on the research questions relating to: health insurance system reforms to improve equity; integration of NCDs prevention strategy into primary health care; cost-effective population-level interventions for NCDs and road traffic injury prevention; tailoring medical qualifications; epidemiological assessment of NCDs by geographic areas; equality in the distribution of health resources and services; current and future common health problems in Iran's elderly and strategies to reduce their economic burden; the status of antibiotic resistance in Iran and strategies to promote rational use of antibiotics; the health impacts of water crisis; and research to replace the physician-centered health system with a team-based one. CONCLUSIONS: These findings highlight consensus amongst various prominent Iranian researchers and stakeholders over the research priorities that require investment to generate information and knowledge relevant to the national health targets and policies. The exercise should assist in addressing the knowledge gaps to support both the National General Health Policies by 2025 and the health targets of the United Nations' Sustainable Development Goals by 2030.

The Role of Doppler Imaging in the Assessment of Right Ventricular Function: a Case-control Study of Acute Inferior Wall Infarction.

BACKGROUND: Right ventricular infarction (RVI) develops in 30-50% of patients with inferior wall infarction (IWI). The rates of mortality, morbidity, and complications in these patients are greater than in the patients without RVI. We compared the tissue Doppler imaging (TDI) indices between a group of patients with IWI and RVI, with a similar group of patients who had IWI alone to investigate the application of TDI indices in the evaluation and detection of right ventricular function. MATERIAL AND METHODS: We studied 49 patients with first acute IWI in two groups. Group 1 (N=24) were patients with IWI and RVI while group 2 consisted of patients with IWI alone (N=25), based on standard electrocardiogram criteria. The peak systolic (Sm), peak early (Em) and late (Am) diastolic velocities, and Em/Am ratio were obtained from the apical four chamber view, at the lateral side of the tricuspid annulus. We measured trans-tricuspid early (ET) and peak (AT) filling velocity, ET/AT ratio, right ventricular end diastolic diameter (RVEDD), and tricuspid annular plane systolic excursion (TAPSE) by M-mode TDI projected at the long axis of parasternal view. RESULTS: The RVEDD and E/Em ratio were increased, while the TAPSE was significantly decreased in the patients with RVI as compared to those without RVI (4.7± 0.6 vs. 3.1±0.2 cm; p < 0.005, 5.6±2.21 Vs 4.5±1.2; p<0.006 and 1.7±0.4 vs. 2.3±0.5 cm; p <0.0001, respectively). However, the other statistically measured parameters were not significantly different between these groups. CONCLUSION: The measurement of RVEDD, E/Em ratio, and TAPSE, as right ventricular myocardial systolic and diastolic parameters by pulse wave TDI could be used to objectively assess the status of RV condition in patients with first acute IWI.

Comparison of Proposed Modified and Original Sequential Organ Failure Assessment Scores in Predicting ICU Mortality: A Prospective, Observational, Follow-Up Study.

Background. The sequential organ failure assessment (SOFA) score has been recommended to triage critically ill patients in the intensive care unit (ICU). This study aimed to compare the performance of our proposed MSOFA and original SOFA scores in predicting ICU mortality. Methods. This prospective observational study was conducted on 250 patients admitted to the ICU. Both tools scores were calculated at the beginning, 24 hours of ICU admission, and 48 hours of ICU admission. Diagnostic odds ratio and receiver operating characteristic (ROC) curve were used to compare the two scores. Results. MSOFA and SOFA predicted mortality similarly with an area under the ROC curve of 0.837, 0.992, and 0.977 for MSOFA 1, MSOFA 2, and MSOFA 3, respectively, and 0.857, 0.988, and 0.988 for SOFA 1, SOFA 2, and SOFA 3, respectively. The sensitivity and specificity of MSOFA 1 in cut-off point 8 were 82.9% and 68.4%, respectively, MSOFA 2 in cut-off point 9.5 were 94.7% and 97.1%, respectively, and MSOFA 3 in cut-off point of 9.3 were 97.4% and 93.1%, respectively. There was a significant positive correlation between the MSOFA 1 and the SOFA 1 (r: 0.942), 24 hours (r: 0.972), and 48 hours (r: 0.960). Conclusion. The proposed MSOFA and the SOFA scores had high diagnostic accuracy, sensitivity, and specificity for predicting mortality.

Helicobacter pylori eradication in West Asia: a review.

The efficacy of first- and second-line Helicobacter pylori (H. pylori) eradication regimens varies considerably in West Asian countries, mainly due to the variable prevalence of resistant organisms. However, no review article has yet evaluated and compared the efficacy of different regimens among different countries of this region. Therefore, we conducted a review to select the best options and provide recommendations for H. pylori treatment in this geographic region. A search through PubMed was carried out to obtain relevant randomized clinical trials published in English language up to June 2013. According to the results, among different therapeutic regimens used as the first-line protocols, 10-d Bismuth-Furazolidone/Metronidazole quadruple therapy, 14-d Clarithromycin-containing hybrid therapy and 14-d quadruple therapy including a proton pump inhibitor + Bismuth + Tetracycline (500 mg QID) + Metronidazole (500 mg TDS) seemed to be appropriate options. Among second-line therapeutic regimens, Bismuth-based quadruple therapies containing Tetracycline and Furazolidone/Metronidazole, triple therapy containing Amoxicillin and Gatifloxacin and Quadruple therapy including Bismuth + Azithromycin and Ofloxacin seemed to be effective options. Third-line therapies were not evaluated in West Asia; most guidelines, however, recommend choosing optimal eradication regimen according to the pattern of antibiotic susceptibility of H. pylori. Although we limited our investigation to H. pylori eradication regimens in West Asia, the clinical significance of the results goes beyond the countries situated in this geographic region. In fact, the results are transferrable to any region as long as the patterns of resistance are the same.

Application of a systems approach to the bottom-up assessment of pharmacokinetics in obese patients: expected variations in clearance.

BACKGROUND AND OBJECTIVES: The maintenance dose of a drug is dependent on drug clearance, and thus any biochemical and physiological changes in obesity that affect parameters such as cardiac output, renal function, expression of drug-metabolizing enzymes and protein binding may result in altered clearance compared with that observed in normal-weight subjects (corrected or uncorrected for body weight). Because of the increasing worldwide incidence of obesity, there is a need for more information regarding the optimal dosing of drug therapy to be made available to prescribers. This is usually provided via clinical studies in obese people; however, such studies are not available for all drugs that might be used in obese subjects. Incorporation of the relevant physiological and biochemical changes into predictive bottom-up pharmacokinetic models in order to optimize dosage regimens may offer a logical way forward for the cases where no clinical data exist. The aims of the current report are to apply such a 'systems approach' to identify the likelihood of observing variations in the clearance of drugs in obesity and morbid obesity for a set of compounds for which clinical data, as well as the necessary in vitro information, are available, and to provide a framework for assessing other drugs in the future. METHODS: The population-specific changes in demographic, physiological and biochemical parameters that are known to be relevant to obese and morbidly obese subjects were collated and incorporated into two separate population libraries. These libraries, together with mechanistic in vitro-in vivo extrapolations (IVIVE) within the Simcyp Population-based Simulator™, were used to predict the clearance of oral alprazolam, oral caffeine, oral chlorzoxazone, oral ciclosporin, intravenous and oral midazolam, intravenous phenytoin, oral theophylline and oral triazolam. The design of the simulated studies was matched as closely as possible with that of the clinical studies. Outcome was measured by the predicted ratio of the clearance of the drug in obese and lean subjects ± its 90% confidence interval, compared with observed values. The overall statistical measures of the performance of the model to detect differences in compound clearance between obese and lean populations were investigated by measuring sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). A power calculation was carried out to investigate the impact of the sample size on the overall outcome of clinical studies. RESULTS: The model was successful in predicting clearance in obese subjects, with the degree to which simulations could mimic the outcome of in vivo studies being greater than 60% for six of the eight drugs. A clear difference in the clearance of chlorzoxazone was correctly picked up via simulation. The overall statistical measures of the performance of the Simcyp Simulator were 100% sensitivity, 66% specificity, 60% PPV and 100% NPV. Studies designed on the basis of the ratio of the absolute values required substantial numbers of participants in order to detect a significant difference, except for phenytoin and chlorzoxazone, where the ratios of the weight-normalized clearances generally showed statistically significant differences with a smaller number of subjects. CONCLUSION: Extension of a mechanistic predictive pharmacokinetic model to accommodate physiological and biochemical changes associated with obesity and morbid obesity allowed prediction of changes in drug clearance on the basis of in vitro data, with reasonable accuracy across a range of compounds that are metabolized by different enzymes. Prediction of the effects of obesity on drug clearance, normalized by various body size scalars, is of potential value in the design of clinical studies during drug development and in the introduction of dosage adjustments that are likely to be needed in clinical practice.

Prevention of coronary heart disease with statins in UK South Asians and Caucasians.

AIMS: To determine the prevalence of subjects eligible for primary and secondary prevention of coronary heart disease (CHD) among the British South Asian population and to compare that with British Caucasians. METHODS AND RESULTS: We used the Health Survey for England 1998 and 1999 datasets, holding data on 9950 Caucasians and 1938 South Asians. Thresholds for treatment were a total cholesterol >3.5 mmol/l and either a history of cardiovascular disease or elevated estimated CHD risk, adjusted where necessary for ethnic differences. Separate analyses were performed for primary prevention risk thresholds of >15% and >30% over 10 years. The prevalence of previous myocardial infarction, angina, or stroke was higher in South Asian men than in Caucasian but the reverse was seen in women. More than 93% [95% confidence interval (CI) 88-97] of South Asian men and nearly 68% (95% CI 66-71) of Caucasian men older than 55 years have a CHD risk greater than 15% (equivalent to cardiovascular risk of 20%) and a cholesterol above 3.5 mmol/l and would be eligible for treatment with lipid-lowering drugs. The equivalent proportions in women are 55% (95% CI 46-65) and 18% (95% CI 16-20) in South Asians and Caucasians, respectively. CONCLUSION: Treating this proportion of the population will have a societal impact, the majority of older people becoming patients, and although it may well be cost-effective for individuals, it will require substantial new resources.